It is now widely recognized that asthma represents the clinical manifestations of airways disease characterized by a unique form of chronic inflammation. Prominent in the inflammatory process are cells within the airways such as mast cells, eosinophils, and T lymphocytes. Asthma is most associated with underlying atrophy, sensitization to inhaled allergens, and elevations in production of immunoglobulin E (IgE). Such allergic and asthmatic responses are associated with the presence of helper T lymphocytes characterized by the production of certain cytokines characterizing the Th2-subset of helper T lymphocytes. Th2 cytokines include interleukin (IL-4), involved in IgE production and the differentiation of Th2 type lymphocytes; IL-5, involved in the recruitment, activation, and survival of circulating eosinophils accumulating in an inflammatory site; and IL-13, sharing many of the properties of IL-4 including stimulating the expression of adhesion molecules on endothelial cells lining the blood vessels. Our work using the model of segmental allergen challenge of the airways in human subjects has demonstrated specific recruitment of eosinophils, basophils, and helper/memory T lymphocytes into the airways in response to allergen challenge of sensitized individuals. These findings indicate selective mechanisms involved in the inflammatory response to allergen as well as the subsequent immunologic sensitization of the airway to exposure on a specific allergen. Underlying the inflammatory response involving recruitment of eosinophils and basophils is the expression and production of Th2 type cytokines including IL-4, IL-5, and IL-13. The mechanisms by which cellualr recruitment occurs has been further examined by studying the effect of systemic corticosteroids on the inflammatory response. Results clearly demonstrate multiple effects of systemic corticosteroids including significant decreases in the number of eosinophils, basophils and T lymphocytes recruited to the site of allergen challenge. These effects on cellular influx were associated with inhibition of kinin generation and plasma exudation as markers of blood vessel and airway permeability. Increased levels of gene expression for IL-4 and IL-5 as well as cytokine-specific protein production was also inhibited by the administration of corticosteroids. Production of E-selectin, one of the adhesion molecules involved in cellular recruitment was also inhibited by corticosteroids. Production of the cytokine IL-2 was also inhibited by steroid administration, while expression of mRNA and production of IFNgamma was not affected. Administration of systemic corticosteroids did not affect the immediate release of histamine and prostaglandin D2 consistent with a lack of effect on mast cell mediator release. These results indicate that many of the mechanisms of recruitment of inflammatory cells involved in allergic inflammation and asthma are inhibited by systemic corticosteroids and are likely to involve mechanisms inhibiting the expression of cytokine genes, cytokine production, and induction of adhesion molecules. Our most recent studies on the mechanisms of cellular recruitment in allergic inflammation in asthma have focused on the recruitment of allergen- specific T cells to the site of allergen challenge. Using subjects sensitized to multiple allergens and challenged at different times with different allergens, i.e., dust mite or ragweed allergens, we have demonstrated that within the purified helper T-cell population is an allergen-specific T cell population detected by allergen-specific responses to allergen stimulation in vitro. By stimulating helper T cell populations with both allergens following different allergen challenges in vivo, we have demonstrated that even within 20 hours, there appears to be an allergen-driven recruitment of previously sensitized T lymphocytes accumulating at the site of inflammation. The results suggest that in addition to mechanisms involving recruitment of inflammatory cells to the site of allergen challenge, there is an allergen- specific component to the cellular response. Such findings suggest that antigen-presenting cells such as macrophages or dendritic cells may be involved in allergen-specific lymphocyte accumulation and immunologic priming of the airway for response to further exposure to allergens. Such mechanisms may be important in the perpetuation and localization of inflammation in the asthmatic airway stimulated by exposure to allergen. Future studies will determine whether it is the allergen-specific T cell population recruited to the site of allergen challenge which is the source of the Th2 cytokine profile demonstrated in the mixed cell population accumulating following allergic challenge.